Worm infections are cause of severe morbidity as diarrhea, malnutrition, anemia, growth/cognitive stunting, liver fibrosis and certain types of cancer. The results of continuous spoiling by parasites is reflected in the difficulty in attention, working and learning which, consequently, lead to a situation of social vulnerability with serious implications in future generations. Studies on helminth infections estimated more than 1.5 billion people were infected in 2018, despite the efforts to treat the disease. There is a need for improvement of multifaceted approaches with multi- and transdisciplinary ways of thinking to change this situation and attain a sustainable disease elimination/control. With holistic approaches as eco-health and one-health to study helminthic diseases, we aim to understand the relationship among the parasite/animal species and the environment determining how each organism fits in a complex network. Then, understanding the biological and cultural aspects of infection, it is possible to design smart and sustainable ways to control the disease locally. We will present our experience using eDNA in eco-health/one-health studies on opisthorchiasis in Laos and schistosomiasis in Madagascar and Philippines where eDNA was successfully used as an important tool to link pathogen and host with high accuracy.